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Multiple Myeloma X-ray, Diagnostic Testing Explained

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Despite the known limitations…conventional radiography (X-rays) still represents the reference standard for diagnosis of MM due to its wide availability and low costs.

The ability of conventional oncology to exactly, specifically diagnose multiple myeloma (MM), is both a great strength and a great weakness of this incurable blood cancer. One the one hand, conventional radiography aka x-rays, are the standard for managing multiple myeloma. On the other hand, when it comes to MM diagnotics, x-rays have limitations that must be taken into account when your oncologist is managing your MM long-term.

In the blog post below, I will make the argument that conventional radiography, x-rays, are a low cost, low toxicity, widely available method for keeping an eye on your bones, your MM, for the long-term but too limited for diagnosing your MM initially. 

One the one hand, MM is difficult to diagnose and is often misdiagnosed or goes UN-diagnosed for months sometimes for years. As a systemic blood cancer, MM can’t really be seen and therefore often goes undiagnosed.

Two common symptoms of living with undiagnosed multiple myeloma is bone damage and anemia resulting in pain and fatigue. Telling your doctor that your back/ribs/hip hurts and that you feel tired all the time is often difficult feedback for the M.D. to act on.

The other challenge faced by myeloma patients and survivors is that once your MM is diagnosed, the disease can be tracked, measured and examined with remarkable specificity. For example, a patient’s m-spike, a widely used blood marker for multiple myeloma, can increase or decrese by several tens sending the patient into despair or joy depending on the direction of this marker.

In fact, an m-spike increasing or decreasing by less than 1 over a several month period is not enough of a change to warrant altering your therapy plan. MM patients really should track several m-spike values over a period of months to determine a trend before changing their therapy plan.

Conventional oncology’s degree of MM diagnosis results in a dizzying list of terms including partial remission, very good partial remission, complete remission, stringent complete remission, minimal residual disease positive or MRD negative.

Bone, Blood, Urine and your Genetic Make-up-The information listed below is a solid general explanation of multiple myeloma diagnostics that offer a basic treatment of what newly diagnosed MM patients need to know about their MM diagnosis.

How specific symptoms or side-effects (a decrease in hemoglobin/RBC leading to fatigue for example) might relate to specific tests should be discussed with with your fellow patients/survivors on Beating Myeloma or with your myeloma specialist.

If you have a question about any of your MM diagnosis, diagnostic testing, please scroll down the page, post a question or a comment and I will reply to you ASAP.

Thank you,

David Emerson

  • MM Survivor
  • MM Cancer Coach
  • Director PeopleBeatingCancer

Recommended Reading:

Imaging of multiple myeloma: Current concepts

CONCLUSION- Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of MM from other monoclonal plasma cell diseases. Despite the known limitations such as low sensitivity, limited specificity and inability to detect extraosseous lesions, conventional radiography (X-rays) still represents the reference standard for diagnosis of MM due to its wide availability and low costs. Besides conventional radiography, newer cross-sectional imaging modalities such as whole-body low-dose CT, whole-body MRI and 18F-FDG PET/CT are available for diagnosis of osseous and extraosseous manifestations of MM.

Among the cross-sectional imaging techniques, whole-body low-dose CT is currently replacing conventional radiography due to its high sensitivity for osseous lesions and the possibility to detect extraosseous lesions. Whole-body MRI and 18F-FDG PET/CT feature the highest sensitivity for osseous lesions, soft tissue lesions and organ manifestations. For that matter, MRI has the highest sensitivity for detection of diffuse bone marrow involvement and 18F-FDG PET/CT for detection of extraosseous lesions. Whole-body MRI should be considered in all patients with inconspicuous conventional radiography, all patients with apparently solitary plasmacytoma and patients with suspicion of spinal cord or nerve root compression…”

Tests to Find Multiple Myeloma

If symptoms suggest that a person might have multiple myeloma, more tests are done.

Lab tests

Blood counts- The complete blood count (CBC) is a test that measures the levels of red cells, white cells, and platelets in the blood. If there are too many myeloma cells in the bone marrow, some of these blood cell levels can be low. The most common finding is a low red blood cell count (anemia).

Blood chemistry tests- Levels of blood creatinine, albumin, calcium, and other electrolytes will be checked.

  • Creatinine levels show how well your kidneys are working. High levels mean that the kidneys are not functioning well. This is common in people with myeloma.
  • Albumin is a protein found in the blood. Low levels can be seen in myeloma.
  • Calcium levels may be high in people with advanced myeloma. High calcium levels (hypercalcemia) can cause symptoms of fatigue, weakness, and confusion.

A blood test to measure lactic dehydrogenase (LDH) levels might also be done. It can be a useful indicator of a patient’s prognosis (outlook). High levels mean the disease is more advanced and may have a worse prognosis.

Urine tests- A routine urine sample is typically taken to look for myeloma protein that has filtered through the kidney. You most likely also will be asked to give a sample of urine that has been collected over a 24-hour period, so it can measure how much myeloma protein is present. These tests are called urine protein electrophoresis (UPEP) and urine immunofixation.

Quantitative immunoglobulins- This test measures the blood levels of the different antibodies (also called immunoglobulins). There are several different types of antibodies in the blood: IgA, IgD, IgE, IgG, and IgM. The levels of these immunoglobulins are measured to see if any are abnormally high or low. In multiple myeloma, the level of one type may be high while the others are low.

Electrophoresis-The antibody produced by myeloma cells is abnormal because it is monoclonal (all the exact same ). Serum protein electrophoresis (SPEP) is a test that measures the antibodies in the blood and can find a monoclonal antibody. Another test, called immunofixation or immunoelectrophoresis, is used to determine the exact type of abnormal antibody (IgG. IgA or some other type). Finding a monoclonal antibody in the blood may be the first step in diagnosing multiple myeloma. This abnormal protein is known by several different names, including monoclonal immunoglobulin, monoclonal protein (M protein), M spike, or paraprotein.

Antibodies are made up of chains of protein : 2 long (heavy) chains and 2 shorter (light) chains. Sometimes pieces of the abnormal myeloma protein are filtered through the kidney into the urine. This urine protein, known as Bence Jones protein, is the part of the antibody called the light chain. The tests used for finding a monoclonal antibody in urine are called urine protein electrophoresis (UPEP) and urine immunofixation. These are done most often on urine that has been collected over a 24-hour period, not just on a routine urine sample.

Serum free light chains- This blood test can measure the light chain levels in the blood and is done when looking for myeloma or light chain amyloidosis.

This is most helpful in the rare cases of myeloma in which no M protein is found by SPEP. Since the SPEP measures the levels of intact (whole) antibodies, it cannot measure the amount of light chains only.

This test also calculates the light chain ratio which is used to see if there is one type of light chain more than the other. There are 2 kinds of light chains: kappa and lambda. Normally, they are present in equal amounts in the blood, giving a ratio of 1 to 1. If there is more of one type of light chain than the other, the ratio will be different, which can be a sign of myeloma.

Beta-2 microglobulin-This is another protein made by the myeloma cells. Although this protein itself doesn’t cause problems, it can be a useful indicator of a patient’s prognosis (outlook). High levels mean the disease is more advanced and may have a worse prognosis.

Types of Biopsies

Bone marrow biopsy- People with multiple myeloma have too many plasma cells in their bone marrow. The procedure used to check the bone marrow is called a bone marrow biopsy and aspiration. It can be done either at the doctor’s office or at the hospital…

The bone marrow tissue is examined in the lab to see the appearance, size, and shape of the cells, how the cells are arranged and to determine if there are myeloma cells in the bone marrow and, if so, how many. The aspirate (the liquid part of the bone marrow) may also be sent for other tests, including immunohistochemistry and flow cytometry, and chromosome analyses, including karyotype and fluorescent in situ hybridization (also known as FISH).

  • Immunohistochemistry: a part of the biopsy sample is treated with special proteins which cause color changes and help identify myeloma cells.
  • Flow cytometry: A sample of bone marrow is treated with special proteins that stick only to certain cells. This can help determine if those cells are abnormal and if they are myeloma cells, lymphoma cells, some other cancer, or a non-cancerous disease.
  • Cytogenetics: A test that evaluates chromosomes (long strands of DNA) in normal bone marrow cells and myeloma cells. Some myeloma cells may have too many chromosomes, too few chromosomes, or other chromosome abnormalities (such as translocations and deletions). Finding these changes can sometimes help in to predicting a person’s prognosis (outlook). Cytogenetic testing usually takes about 2 to 3 weeks to get a result.
  • Fluorescent in situ hybridization (FISH): It uses special fluorescent dyes that only attach to specific parts of chromosomes. It can find most chromosome changes (such as translocations and deletions) that can be seen in the lab in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing. It’s very accurate and results are often available within a couple of days.

Fine needle aspiration biopsy- Fine needle aspiration (FNA) uses a very thin needle and a syringe to withdraw a small amount of tissue from a tumor or lymph node. The doctor can aim the needle while feeling an enlarged lymph node near the surface of the body. If the abnormal area (tumor) is deep in the body, the needle can be guided while it’s watched on a computed tomography (CT) scan (see discussion of imaging tests later in this section). The main advantage of FNA is that it doesn’t require surgery. The disadvantage is that in some cases the thin needle cannot remove enough tissue for a definite diagnosis.

Core needle biopsy- This test is similar to FNA, but a larger needle is used and a larger tissue sample is removed.

If an area looks abnormal on an x-ray, a biopsy may be needed to confirm that it’s a plasmacytoma. Most often, a needle biopsy (fine or core) is used.

Imaging tests- Imaging tests use sound waves, x-rays, magnetic fields, or radioactive substances to create pictures of the inside of your body. Imaging tests may be done for a number of reasons, such as:

  • To look at suspicious areas that might be cancer
  • To learn how far cancer has spread
  • To help determine if treatment is working

Bone x-rays- X-rays can detect bone destruction caused by the myeloma cells. Often doctors will do a series of x-rays that includes most of the bones. This is called a bone survey or skeletal survey.

CT scan (Computed tomography scan)- A CT scan uses x-rays taken from different angles, which are combined by a computer to make detailed pictures of the organs. Sometimes, this test can help tell if your bones have been damaged by myeloma. It can also be used to guide a biopsy needle into an area of concern.

Magnetic resonance imaging (MRI) scans- Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. A contrast material called gadolinium may be injected into a vein before the scan to see details better.

MRI scans are very helpful in looking at bones, the brain, and the spinal cord. Because MRI can find plasmacytomas that can’t be seen on regular x-rays, they can be helpful if the patient has pain in a bone but nothing abnormal is seen on the x-ray. MRI can also be used to look at the bone marrow in patients with multiple myeloma.

Positron emission tomography (PET) scans-For this test, a form of radioactive sugar is put into a vein and travels throughout the body. Cancer cells absorb high amounts of this sugar. A special camera then takes pictures that show the areas where the sugar collected throughout the body. A PET scan is often combined with a CT scan (known as a PET/CT scan).

When a patient appears to have a solitary plasmacytoma, a PET scan may be used to look for other plasmacytomas. Like MRI scans, PET scans can find plasmacytomas that can’t be seen on regular x-rays, so they are helpful if the patient has pain in a bone but the x-ray result is negative.

Echocardiogram (ECHO)- Amyloidosis often affects the heart, so if your doctor diagnoses or suspects you have this disorder, an echocardiogram (ECHO) may be ordered. This test is basically an ultrasound of the heart. It uses sound waves to look at the heart muscle and how well it’s working. The echocardiogram can see if the heart size is normal and if it is pumping normally. It also is especially helpful if amyloid is suspected because amyloid in the heart muscle looks different from normal heart muscle.

Diagnosing Multiple Myeloma-Multiple myeloma is often diagnosed based on tests, the patient’s symptoms and the doctor’s physical exam of the patient. A diagnosis of multiple myeloma requires either:

1. A plasma cell tumor (proven by biopsy) OR at least 10% plasma cells in the bone marrow AND

2. At least one of the following:

  • High blood calcium level
  • Poor kidney function
  • Low red blood cell counts (anemia)
  • Holes in the bones from tumor found on imaging studies (CT, MRI, PET scan)
  • Increase in one type of light chain in the blood so that one type is 100 times more common than the other
  • 60% or more plasma cells in the bone marrow

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